Antibiotic resistance in S.typhi

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A gram-negative, flagellated, facultatively anaerobic bacillus called S. typhi has three main antigens: the flagellar antigen (H), the somatic antigen (O), and the vi antigen. The organism often transitions from one phase to another. H antigen can be present in either or both of the two phases. O antigens are found on the exterior of the membrane. Overlying the O antigen, the Vi antigen is a surface antigen. Salmonellae are distinguished from S.typhi by the Vi antigen.

S. typhi is a pathogen that is effective due to a variety of traits. This species possesses a Gram-negative organism-specific endotoxin in addition to the Vi antigen, which is expected to boost virulence.

History of AMR in S.typhi: 

Chloramphenicol was the most efficient and widely used treatment for typhoid fever when it was first discovered. Due to its widespread and indiscriminate use, chloramphenicol-resistant S. typhi isolates were discovered in England within two years. These strains were also resistant to ampicillin. co-trimoxazole was a successful alternative medication until co-trimoxazole-resistant strains were discovered in France. Despite the paucity of safety evidence, pediatricians worldwide were forced to employ ciprofloxacin in the late 1980s due to the epidemic of antibiotic resistance.

Fluoroquinolones consequently became the preferred medication for treating MDRTF all over the world. However, soon after, there were reports of S. typhi isolates that were resistant to fluoroquinolones. With the development of quinolone (nalidixic acid) resistance, third-generation cephalosporins were used for treatment, and reports of resistance to them also followed.

Mechanisms of AMR in S.typhi:

Following are some methods that S.typhi resists the effects of antibiotics.

• Antimicrobial agent inactivation
• Transport or efflux of the antibiotic
• Antimicrobial target site modification
• Decrease in the antibacterial agent's permeability

Antimicrobial agent inactivation:

This is a typical reason why antimicrobial agents are destroyed or become activated. The bacterial pathogens prevent attacks by chemically altering medications to keep them inactive. The initial strains of antibiotic-resistant  S.typhi carried chloramphenicol acetyltransferase type I, which encodes an enzyme that inactivates chloramphenicol via acetylation.

Transport or efflux of the antibiotic:

This resistance mechanism works by pumping the drug out of the cell after it has entered. Certain pathogens have efflux pumps, or plasma membrane translocases, which eliminate medicines. These transport proteins are sometimes referred to be multi-drug resistance (MDR) pumps because they are generally non-specific and may pump a wide variety of medicines, including quinolones.

Antimicrobial target site modification:

Resistance develops when the pathogen's target enzyme or cellular structure is altered to the point where it is no longer susceptible to treatment. S. typhi and other sulfonamide-resistant bacteria possess this mechanism. The enzyme produced by these organisms has a very strong affinity for PABA and a very weak affinity for sulfonamide. Thus, the enzymes function sufficiently to allow the bacterium to function even in the presence of sulfonamides.

Decrease in the antibacterial agent's permeability:

Often, pathogens develop resistance just by blocking the drug's entry. This pathway has led to tetracycline, quinolone, and certain aminoglycoside resistance in S. typhi. A decrease in permeability can also lead to sulfonamide resistance.